Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07J—STEROIDS
  • C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
  • C07J1/0051—Estrane derivatives
  • C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
  • C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified

Definitions

• the invention relates to the objects characterized in the claims.
• An acyl group R in formula I is to be understood as the residues of acids customary in steroid chemistry.
• Examples include the residues of organic carboxylic and sulfonic acids with 1 to 17 carbon atoms, preferably of organic carboxylic acids with 1 to 7 carbon atoms, such as formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, hexanoyl, heptanoyl, chloroacetyl, glycoloyl, succinyl, Glutaryl, adipoyl, benzoyl etc.
• Alkyl groups with the meaning of R should preferably contain 1 to 5 carbon atoms and may be interrupted by an oxygen atom.
• Examples of the alkyl group R which may be interrupted by an oxygen atom are methyl, ethyl, methoxymethyl, methoxyethyl, ethoxyethyl, propyl, butyl, pentyl, etc.
• the new compounds of general formula I have strong antiandrogenic effects.
• 16ß-ethyl-17ß-hydroxy-4,9 (l0) -estradien-3-one is more effective than the corresponding steroid saturated in the 9 (10) position.
• the inhibition of the increase in the seminal vesicle and prostate weight of rats caused by testosterone propionate after subcutaneous administration was determined.
• the 16 ⁇ -ethyl-17ß-hydroxy-4,9 (10) -estradien-3-one (A) according to the invention with 0.3 mg per animal and day is significantly more effective than the 16ß-ethyl known from German patent specification 2 100 319 17 ⁇ -hydroxy-4-estren-3-one (B).
• the compounds according to the invention are well suited for the treatment of diseases which are caused by androgens or are dependent on androgens.
• the compounds of general formula I can be used to treat age-related prostatic hyperplasia in amounts of approximately 10 to 200 mg / day. Treatment for acne, hirsutism and alopecia are also possible.
• the active ingredients can be processed with the additives, carrier substances and / or taste correctants customary in pharmaceutical pharmacy to form the usual forms of administration according to methods known per se.
• Tablets, dragees, capsules, pills, suspensions or solutions are particularly suitable for the preferred oral application.
• Oily solutions such as sesame oil or castor oil solutions are suitable for parenteral, in particular intramuscular, application.
• solubilizers such as Benzyl benzoate or benzyl alcohol can be added.
• the concentration of the active substances in oily solution is approximately 10-200 mg / ml.
• the process characterized in claim 7 for the preparation of the compounds of the general formula I is carried out in a manner known per se.
• the bromination and dehydrobromination of the compound according to formula II is preferably carried out with pyridine hydrobromide perbromide in the presence of an organic base.
• suitable organic bases are pyridine, collidine or triethylamine.
• Pyridine is preferably used and the process is carried out at about 0 to 100 C.
• the additional double bond is introduced with formation of the ⁇ 4.9 (10) grouping.
• esterification of the free 17 ⁇ -hydroxy group in the compound according to formula I can be carried out by treatment with a reactive acid derivative, for example an acid anhydride or halide, in the presence of a base such as pyridine, 4-dimethylaminopyridine or collidine at temperatures of about 20 to 120 ° C. respectively.
• a reactive acid derivative for example an acid anhydride or halide
• a base such as pyridine, 4-dimethylaminopyridine or collidine at temperatures of about 20 to 120 ° C. respectively.
• Alkylating compounds such as alkyl hologenides, are used to etherify the 17 ⁇ -hydroxy group.
• the etherification is carried out in a manner known per se in the presence of a strong base, such as sodium hydroxide solution, using a polar solvent, such as hexamethylphosphoric triamide, at 0-50 C or in the presence of a strong base, such as sodium hydride, using an ether, such as tetrahydrofuran 30 - 100 ° C.
• the hydroxy compound is converted into the corresponding tetrahydrophyranyl or alkoxyethyl ether with dihydropyran or alkyl vinyl ethers in the presence of a strong acid, such as p-toluenesulfonic acid or phosphorus oxychloride.
• the reaction is preferably carried out in the presence of inert solvents, such as chloroform, dichloromethane, tetrahydrofuran, dioxane, etc., at a reaction temperature of from -20 ° C. to 100 ° C.
• methoxymethyl ethers the hydroxy compound is reacted, for example, with formaldehyde dimethyl acetal in anhydrous dichloromethane in the presence of phosphorus pentoxide at room temperature.
• a solution of 2 g of 16 ⁇ -ethyl-17ß-hydroxy-4,9 (10) -estradien-3-one in 30 ml of toluene is added after adding 5 g of caproic anhydride and 2.5 g of 4-dimethylaminopyridine at 60 ° C for 3 hours touched. Then poured into saturated NaHCO 3 solution and extracted with ethyl acetate. After chromatography of the crude product on silica gel with hexane / ethyl acetate O 20%, 1.8 g of 16 ⁇ -ethyl-17 ⁇ -hexanoyloxy-4.9 (10) -estradien-3-one with a melting point of 74-76 C (from hexane) are obtained. .

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Steroid Compounds (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Publications (2)

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ID=6107923

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Country Status (4)

Cited By (2)

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Citations (2)

• 1980
  • 1980-07-21 DE DE19803027908 patent/DE3027908A1/de not_active Withdrawn
• 1981
  • 1981-07-11 AT AT81105433T patent/ATE5413T1/de not_active IP Right Cessation
  • 1981-07-11 DE DE8181105433T patent/DE3161500D1/de not_active Expired
  • 1981-07-11 EP EP81105433A patent/EP0044495B1/fr not_active Expired
  • 1981-07-20 JP JP56112387A patent/JPS5753499A/ja active Granted

Patent Citations (2)

Non-Patent Citations (1)

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